The invention relates to cosmetic compositions for topical application for counteracting UV radiation induced skin damage comprising as active substances a first component obtained from inactivated cultures of a bacteria selected from the genus Bifidobacterium, Actinomycetaceae, Propionimycetaceae, Lactobacillaceae and Coryneform bacteria and a second component which is an extract of plant extracellular matrix. Preferably, the plant extracellular matrix is selected from the group consisting of glycoproteins, carbohydrate polymers and arabinogalactan proteins. Processes for using the cosmetic compositions are also described.
Exposure of skin to UV radiation can cause diverse biological effects, including sunburn (inflammation), induction of skin cancer (melanoma), premature skin aging and alteration in cutaneous immune cells (immunosuppression) all leading to (permanent) damage of the skin cells. Skin cell damage due to UV is induced by several mechanisms, such as UV-induced immunosuppression, UV-induced DNA-damage and accumulation of DNA-damage.
Immunosuppression is a status of immunological imbalance of the skin (Kripke, 1984; Baadsgard, 1991). It is known that cutaneous exposure to UVB (280-320 nm) radiation induces systemic suppression of T-cell mediated contact hypersensitivity (CHS) to haptens and delayed type hypersensitivity (DTH) responses to protein antigens such as Herpes simplex virus, Candida albicans or mycobacteria (Otani et al., 1987; Giannini, 1986; Denkins et al., 1989; Jeevan et al., 1989). Especially Langerhans cells (LC) which are highly specialized antigen-presenting cells (APC) play an essential role in the induction of immune responses to contact allergens, viral antigens and probably cutaneous tumor antigens (Teunissen, 1992). UVB radiation was shown to decrease the number of LC in the epidermis.
Ratis et al., 1998, have shown that exposure to UVB affects LC in at least two distinct pathways. Intercellular adhesion molecules-1 (ICAM-1) and especially CD 86 expression is significantly decreased. In addition, LC viability is reduced, which leads to apoptotic cell death. Both mechanisms contribute to UVB-induced immunosuppressive effects.
Besides LC, keratinocytes (KC) play an important role in UV-induced immunosuppression. UV-light affects production and secretion of immunomodulatory cytokines from KC, depending on its wavelength. Particularly IL-10 expression has been shown to play a major role in the induction of systemic immunosuppression and differential activation of T-helper subsets. Shreedar et al., 1998, described that prostaglandin E2 (PGE2) release of irradiated KC induces serum IL-4 which again induces IL-10 release. Thus, UV exposure activates a cytokine cascade resulting in systemic immunosuppression.
Recent results have demonstrated that UVA radiation also contributes to immunosuppression through an oxidative pathway (Iwai et al., 1999), suppressing the antigen-presenting function of epidermal cells, accompanied with suppression of the expression of costimulatory molecules on LC. It is postulated that this effect is mediated by reactive oxygen species.
Several hazardous effects are mediated by the immunosuppressive properties of UV radiation, as induction of apoptosis or programmed cell death. Apoptotic cells in the skin are called xe2x80x9csunburn cellsxe2x80x9d (Daniels et al., 1961; Young, 1987). Sunburn cells show some characteristic morphological changes: the dilated endoplasmatic reticulum forms vacuoles, chromatin is digested and condenses along the nuclear membrane often forming spheres, and dramatic cell shrinking is the most prevalent characteristic of apoptotic sunburn cells.
Numerous genes that encode mediators which regulate apoptosis have been identified, among them the tumor suppressor gene p53 and apoptosis inhibitor gene bcl-2 which are considered to play important roles. Wang et al., 1998, postulated that UVA and UVB initiate apoptosis by triggering two different signal transduction pathways. Whereas UVA, generating reactive oxygen speciesxe2x80x94mainly singlet oxygenxe2x80x94that cause lipid peroxidation (Kane et al., 1993) and disruption of membrane permeability, leads to immediate apoptosis through down-regulation of bcl-2 expression, UVB causes delayed apoptosis characterized by induction of DNA damage in the form of pyrimidine dimers and subsequent expression and accumulation of p53 proteins. There is increasing evidence that apoptosis may play an important role in immune reaction (Lynch et al., 1995).
Classical UV skin protectors which are used as sunscreens absorb UVA or UVB radiation directly on the skin surface. The protection provided is expressed by their Sun Protection Factor (SPF), which is the minimal dose at which an erythema is observed (Minimal Erythema Dose, MED) and which is highly dependent on the user""s skin type. The use of such sunscreens is limited in that they only provide a certain degree of protection while being directly exposed to the sun. They have no regenerative effect, nor can they interact or prevent any UV-induced biochemical changes in the skin.
For a comprehensive photoprotection, especially against premature skin aging, photoallergies, immunosuppression and skin cancer, it is however necessary to reverse or reduce UV-induced biochemical changes in the skin. JP 05-017363 describes the anti-inflammatory effect produced by Lactobacillus, Bifidobacteria or their cell walls in relation to sunburn.
It is well established that UV exposure may cause dimerization of two adjacent pyrimidine molecules of the DNA. A cell-endogenous, enzymatically controlled excision repair system is able to repair such a damage as long as the damage frequency does not exceed the physiological repair capacity. If the repair capacity is insufficient, which could be the case in aging skin or after excessive UV exposure, cells with unrepaired DNA could be able to survive. The consequence can be chronic photodamage like dermal functional disorders with resultant premature aging, development of a precancerous stage of the cells or final development of skin carcinomas.
EP 0 043 128 B1 and U.S. Pat. No. 4,464,362 describe a cosmetic composition promoting the DNA repair process of the skin and which contains inactivated cultures of Bifidobacteria or bacteria related to this genus. Based on comprehensive in vitro and in vivo tests in animals as well as humans it has been established that the above composition, topically applied, significantly increases the DNA repair rate in UV-damaged cells. The above repair composition is a significant contribution to the art in that for the first time an agent is provided which can effectively prevent UV-induced DNA damage in skin cells.
As discussed above, however, UV-induced skin damage involves a cascade of pathophysiological events and is not limited to DNA damage. In the past few years it became apparent that UV-induced suppression of cell mediated immunity is another very important factor contributing to permanent skin damage including development of skin cancer and premature skin aging.
Fischer et al., 1998, describe molecular mechanisms of photoaging. UVR exposure results in the stimulation of cytokines released from keratinocytes or dermal fibroblasts. This leads to the activation of protein kinase signal transduction cascades, with the consequence of activation of transcription factor AP-1 which induces expression of matrix metalloproteinases (MMP). MMP""s degrade the extracellular matrix in the dermis. ECM damage is followed by matrix repair, which is imperfect and thereby results in premature photoaging of the skin.
Thus, the problem underlying the present invention is to provide a cosmetic composition having significantly improved properties in that it minimizes or prevents chronic UV-induced photodamage in the skin on the DNA level by promoting the endogenous DNA repair mechanism as well as on the immunological level.
The invention relates to cosmetic compositions having an improved regenerative and protective effect on epidermal and dermal cells and their extracellular environment. Such compositions comprise a novel active complex of active ingredients, optimized to protect the skin from potentially harmful environmental effects.
The ingredients of the active complex according to the invention comprise inactivated bacteria selected from the group consisting of the genus of Bifidobacterium, Actinomycetaceae, Propionimycetaceae, Lactobacillaceae and Coryneform bacteria and a plant extracellular matrix composition, preferably prepared from soybean. The invention also provides a process for using such cosmetic compositions comprising the step of topically applying the cosmetic composition to the skin in order to prevent UV radiation induced damage.